Carbanions enolates

An important feature of aldol addition is that carbon-carbon bond formation occurs between the a carbon atom of one aldehyde and the carbonyl group of another This is because carbanion (enolate) generation can involve proton abstraction only from the a carbon atom The overall transformation can be represented schematically as shown m Figure 18 5... 

This involves an aryl carbanion/enolate anion (64), and also eCQ3 derived from the action of strong bases on HCC13 (p. 267), though the latter has only a transient existence decomposing to CC12, a highly electron-deficient electrophile that attacks the aromatic nucleus ... 

Elimination reactions (Figure 5.7) often result in the formation of carbon-carbon double bonds, isomerizations involve intramolecular shifts of hydrogen atoms to change the position of a double bond, as in the aldose-ketose isomerization involving an enediolate anion intermediate, while rearrangements break and reform carbon-carbon bonds, as illustrated for the side-chain displacement involved in the biosynthesis of the branched chain amino acids valine and isoleucine. Finally, we have reactions that involve generation of resonance-stabilized nucleophilic carbanions (enolate anions), followed by their addition to an electrophilic carbon (such as the carbonyl carbon atoms... 

All prepared magnesium enolates 17 are stable in refluxing diethyl ether. Deuteriation, and reactions with various electrophiles confirm their structure (see section HI). It is noteworthy that the lithiated carbanion-enolate analogue, directly obtained by deprotonation of an a-ketoester 18 with lithiated bases (LDA, for example), is not stable and immediately degrades in the medium, whatever the temperature. Comparatively, the magnesium chelate 17 shows a higher stability, which allows its preparation and synthetic applications. 

Three base-catalyzed reactions of such a H s are shown in Fig. 17-1. Since the reactions have the same rate expression, they have the same rate-determining step the removal of an a H to form a stabilized carbanion-enolate anion. The name of this anion indicates that the resonance hybrid has negative charge on C (carbanion) and on O (enolate). 

Problem 17.1 Show how the stable carbanion-enolate anion reacts to give the three products shown in Fig. 17-1. -4... 

Carbanion-enolates are nucleophiles that react with alkyl halides (or sulfonates) by typical S 2 reactions, Carbanion-enolates are best formed using lithium diisopropylamide (lda), (r-Pr)2N Li, in tetrahydrofuran. This base is very strong and converts all the substrate to the anion. Furthermore, it is too sterically hindered to react with RX. 

Since the carbanion-enolates are ambident ions with two different nucleophilic sites, they can be alkylated at C or at O. 

Problem 17.10 (a) Use carbanion-enolate alkylations to synthesize (i) 2-ethylbutanenitrile, (ii) 3-phenyl-2-pentanone, (iii) 2-benzylcyclopentanone. (6) Why can the unsymmetrical ketone in part (ii) be alkylated in good yield "4... 

IVhen treated with 1 mol of 1° RX, the more basic terminal carbanion is alkylated, not the less basic nterior carbanion. The remaining carbanion-enolate can be protonated. 

Stable carbanion-enolates can also serve as the nucleophile. 

A condensation reaction leads to a product with a new C—C bond. Most often the new bond results from a nucleophilic addition of a reasonably stable carbanion-enolate to the C=0 group (acceptor) of an aldehyde less frequently the 0=0 group belongs to a ketone or acid derivative. Another acceptor is the C=N group of a nitrile. 

The addition of the nucleophilic carbanion-enolate, usually of an aldehyde, to the C=0 group of its parent compound is called an aldol condensation. The product is a /3-hydroxycarbonyl compound. In a mixed aldol condensation the carbanion-enolate of an aldehyde or ketone adds to the 0=0 group of a molecule other than its parent. The more general condensation diagramed above is termed an aldol-type condensation. Since the C, not the O, is the more reactive site in the hybrid, the enolate contributing structure is usually omitted when writing equations for these reactions. This is done even though the enolate is the more stable and makes the major contribution. 

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